Arrangement for integrated and automated dna or protein analysis in a single-use cartridge, method for producing such a cartridge and operating method for dna or protein analysis using such a cartridge

ABSTRACT

A cartridge (card) having a system of microchannels and/or microcavities is used for automated DNA or protein analysis. In at least one embodiment, the microchannels or microcavities include geometrical structures for receiving dry reagents. For the purpose of industrial production, the cartridge is produced from a flat card support, e.g., by injection moulding. The reagents are spotted into the open channels, dried and then the channels are sealed by way of a film. A finished cartridge can thus be provided with a test sample and the fully automated measuring sequence can be initiated by inserting said cartridge into a read-out device.

PRIORITY STATEMENT

This application is the national phase under 35 U.S.C. § 371 of PCTInternational Application No. PCT/EP2005/055303 which has anInternational filing date of Oct. 17, 2005, which designated the UnitedStates of America and which claims priority on German Patent Applicationnumber 10 2004 050 576.4 filed Oct. 15, 2004, the entire contents ofwhich are hereby incorporated herein by reference.

FIELD

Embodiments of the invention generally relate to an arrangement forintegrated and automated DNA or protein analysis in a single-usecartridge. Herein, a flat card in check card format is described as acartridge. In addition, embodiments of the invention generally relate tothe production of such a cartridge. Finally, embodiments of theinvention also generally relate to an operating method for DNA orprotein analysis using such a cartridge.

BACKGROUND

For nucleic acid analysis, for example for the analysis of white bloodcells from whole blood with the aim of answering human genome questions,firstly, in a first stage as the sample preparation step, the cells mustbe broken up and then the DNA thus liberated must be isolated. In asecond stage, a PCR (Polymerase Chain Reaction) for selective DNAmultiplication (amplification) is performed in order to increase theconcentration of the DNA to be detected sufficiently for it to bedetectable in a third stage.

In the laboratory, the latter component processes are carried outseparately according to the known state of the art. The three stagesmentioned above each include several working steps and are carried outindependently of one another with different equipment. The individualwork steps are largely performed manually.

The implementation of these steps is dependent on the presence oflaboratory equipment—such as a cell disintegration apparatus, a PCRdevice (so-called thermocycler), possibly a PCR device which is suitablefor quantitative PCR, an electro-phoresis apparatus, a hybridizationstage, an optical reader, so-called Eppendorf tubes, several pipettingdevices and a refrigerated container for reagents, and must be carriedout by trained personnel with observation of safety procedures withregard to infection risk, waste disposal or the like. In particular,several volumetric, i.e. accurate, dispensings (pipettings) of reagentsolutions must be performed. Such work steps are time-consuming andcost-intensive.

From the state of the art, devices for biochemical analysis are knownwhich according to WO 02/073153 A1 make use in particular ofsilicon-based measurement modules, which can be integrated into a chipcard. Moreover, according to WO 02/072262 A1, the reagents used for theanalysis are already integrated into the analysis module in dry-storedform.

SUMMARY

At least one embodiment of the invention is directed to theimplementation of an inexpensive, simply manageable, complete DNA orprotein analysis process in a miniaturized cartridge. In particular inat least one embodiment, the following improvements compared to thelaboratory method should be implemented:

-   -   complete integration of all substances (possibly except for        water) in a closed, single-use cartridge;    -   preparation of the reagents in a form stable on storage at room        temperature;    -   automatic implementation of all processes in the cartridge;    -   no manual working steps, apart from injection of the sample to        be analyzed, e.g. blood;    -   no direct contact with substances hazardous to health (blood and        reagent wastes remain in the cartridge);    -   cartridge geometry allows efficient and rapid thermocycling;    -   all detection processes should operate electrically and be easy        to read;    -   the cartridge used is small and inexpensive to produce.

At least one embodiment of the invention is in particular based on WO02/072262 A1 and the further state of the art mentioned there. Thereinis described an analytical device with reagents stable at roomtemperature, dry-stored in fluid channels, which are brought intosolution through the introduction of water shortly before their use asintended. At least one embodiment of the invention is further based onthe unpublished DE 10 2004 021780 A1 and the unpublished DE 10 2004021822 A1. In addition, the specific use of electrically readabledetection modules is also known.

In contrast to this, an object of at least one embodiment of theinvention is such a single-use cartridge with a system of microchannelsand/or microcavities for a predefined process sequence after sampleuptake, wherein the cartridge has structures to accommodate the dryreagents and devices for the implementation both of the celldisintegration on the one hand and of the PCR on the other, but also ofthe electrochemical detection, are allocated to these structures. Inparticular, the channels therein have different, problem-adaptedstructures. Specifically, the disintegration channel advantageously hasstepped cross-sections for optimal wetting with the dry reagent, whilethe PCR chamber and the Elisa reagent channels have pot-shapeddepressions.

It can thus be achieved that the introduction and preparation of thesample, the DNA amplification and the actual detection of the DNA ispossible in the course of one process.

By way of the system of geometric structures in the micro-channels ormicrocavities to accommodate dry reagents according to at least oneembodiment of the invention, suitable conditions are obtained for DNAanalysis on the one hand and protein analysis on the other. In at leastone embodiment, the following features and measures are essential:

-   -   the reagents introduced into the microchannel or into the        microcavity are dryable substances with negligible vapor        pressure. As the substances are stable at room temperature,        their properties for cell disintegration and/or PCR and/or        detection are retained. In addition, mixtures of the substances        with additives can form thin films, and the mixtures can be        water-tightly covered with thin layers of paraffin wax.

In at least one embodiment of the invention, the reagents and additivesare already introduced as dry substances into depressions of thecartridge channels during production. The following advantages resultfrom this:

-   -   simple and precise application of the reagents during the        production of the cartridge;    -   protection of the reagents during the filling of the reagent        channels, i.e. the reagents are not washed away during a        so-called water flow, but are retained during the filling of the        whole channel. Only after the filling of the channel do the        reagent spots dissolve by diffusion processes and a homogeneous        solution is produced.

In a further example embodiment, the depressions are located atpredefined intervals along the reagent channel. Here, the intervals canbe equidistant or particularly advantageously can be arranged invariable spacing patterns.

The depressions can advantageously be filled with variable quantities ofdry reagent. Through the combination of different amounts of dry reagentand spacing patterns of the depressions, the desired concentrationprofiles of the finished reagent solutions can be established.

For certain functions, such as for example cell disintegration in thepresence of magnetic beads and lysis reagents, an even distribution ofthe insoluble components, i.e. the beads, in the dry reagent isnecessary. For this, the magnetic beads are dispensed into the lysischannel as a suspension. On evaporation of the solvent, it is observedthat the beads are drawn back into the edge region of the lysis channeland an even distribution does not result from this. Through steppedstructuring of the lysis channel cross section, the magnetic beadsdistribute themselves across the steps and an even distribution isachieved.

In order that a cell disintegration, a PCR and a so-called DNA/proteinELISA test can equally be performed with the cartridge according to theinvention, it is advantageous that substrates with DNA-bindingproperties, in particular the DNA-binding magnetic beads, be present inthe microchannels or microcavities. Here, the lysis reagents and themagnetic beads can be contained together in a single dry matrix.Further, the reagents for an ELISA assay are also present in the card.In particular, for the ELISA assay two reagents are needed, i.e. alabeling enzyme as the first reagent and an enzyme substrate as thesecond reagent.

In particular, a detection module for the electrical detection of thehybridization processes is arranged in the cartridge. The detectionmodule advantageously consists of a noble metal/plastic composite or asemiconductor-processed silicon chip with noble metal electrodes.Especially suitable for electric detection here are electrochemical,magnetic or piezoelectric measurement procedures.

For the application of at least one embodiment of the invention, inparticular an input port for a whole blood sample is present in thecartridge according to at least one embodiment of the invention.Moreover, device(s) for the addition of water are present, for exampleinlet ports for connection to an external water supply or an integratedwater reservoir. In the microchannels or microcavities, dry buffersubstances have defined ionic strength after the addition of water.

In the application of at least one embodiment of the invention for theanalysis of white blood cells from whole blood, device(s) for mixing ofa whole blood sample with water or a buffer solution are advantageouslypresent. At the same time, device(s) for passing blood or blood/watermixtures or blood/buffer mixtures through the micro-channel ormicrocavity coated with lysis/bead/reagent are present.

Further, for the PCR to be performed in the cartridge according to atleast one embodiment of the invention during use specifically for DNAanalysis, device(s) for generation of a magnetic field forimmobilization of the DNA/magnetic bead complex in a PCR cavity arepresent. For this purpose, the PCR cavity must be capable of beingsuitably sealed and device(s) for thermocycling must be present.

Finally, in the cartridge according to at least one embodiment of theinvention, it is essential that device(s) for storage of used samplematerial and used reagents be present, which constitute wastereservoirs. At the same time, the device(s) must be suitable for thegermproof, cell-free and particle-free venting of at least one wastereservoir. Finally, for the reading of the cartridge in a reader device,which is not an object of at least one embodiment of the invention,device(s) for the immobilization of the cartridge must be present.

BRIEF DESCRIPTION OF THE DRAWINGS

Further details and advantages of embodiments of the invention followfrom the following descriptions of the diagrams of practical examples onthe basis of the drawings in combination with the patent claims. Indiagrammatic form, respectively:

FIG. 1 shows a cartridge with an overview of individualmicrochannel/microcavity systems with the relevant functiondesignations,

FIG. 2 shows a top view of a cell disintegration channel,

FIG. 3 shows the cross section through the cell disintegration channelaccording to FIG. 5,

FIG. 4 shows two alternatives for the throughflow channel cross section,shown enlarged,

FIG. 5 shows the top view of the PCR chamber in FIG. 1,

FIGS. 6 and 7 show the cross section through the PCR chamber accordingto FIG. 5,

FIG. 8 shows the top view of an ELISA reagent channel in FIG. 1,

FIGS. 9 and 10 show the cross section of the ELISA reagent channelaccording to FIG. 8 and

FIGS. 11 to 23 show the top view of the cartridge according to FIG. 1 invarious process states during an automated evaluation.

In the figures, the same or similarly operating components have the samereference symbols. In particular, FIGS. 1 to 10 are described together,and FIG. 11 to are described together.

DETAILED DESCRIPTION OF THE EXAMPLE EMBODIMENTS

FIG. 1 shows a cartridge 100 for an ELISA (“Enzyme Linked Immuno SorbentASSAY”) test with a front view of the micro-channel or microcavitysystem present therein, wherein for clarity the relevant functiondesignations are also shown. In detail, the cartridge 100 consists of aplastic base 101 with fluidic structures incorporated therein, which arecovered by a plastic film. The structures are further described below onthe basis of FIGS. 2 to 10.

In the top view according to FIG. 1, there can be seen a sample port 102with a dispensing section 105 connected thereto, through which liquidsamples in particular for nucleic acid analysis, for example for theanalysis of white blood cells from whole blood, for answering humangenome questions can be introduced in a defined manner. This isconnected to a channel area 110 for the cell disintegration of thesample and moreover specifically for a DNA analysis an area 120 for aPCR (Polymerase Chain Reaction) for selective DNA multiplication(amplification) in order to increase the concentration of the DNA to bedetected sufficiently for it to be detectable in a third stage. Theactual PCR chamber is sealable by valves 122 and 122′. The detection ofthe samples thus prepared, in particular according to the ELISA method,then takes place in the area 130.

Also visible in FIG. 1 are water ports 103 to 103′″. Through these,water can be introduced into the cartridge 100 as a transport agent andsolvent during the preparation of a sample. Further, venting ports 104to 104′″ are present.

As mentioned, the cartridge 100 has in particular an input port 102 fora whole blood sample. In addition, at least one device for theintroduction of water is present. An inlet port for connection to anexternal water source can be present, or the feed port can be connectedto an integrated water reservoir.

In the normal case, the microchannels or microcavities 101 to 131 arefilled with dry buffer substances which ensure a defined ionic strengthafter the introduction of water. For blood analysis, at least one devicefor mixing of whole blood samples and water or the buffer solutionand/or at least one device for passing a flow of blood or blood-water orblood buffer mixture through a micro-channel coated with a lysis beadreagent or the microcavity are present.

In the channel system, wide regions 106, 107, 108 and 109 are providedas reservoirs to accommodate waste. Apart from this, a region withchannels 131 or 131′ to accommodate different ELISA reagents is present.

In each of FIGS. 2 to 4, reference symbols 101 again indicate thecartridge base. The base contains a throughflow channel 111 shaped in aparticular way especially for cell disintegration (“lysis”) withstep-shaped depressions 112 formed by the side edges to accommodatereagents. Here the depressions 112 have several steps with step heightsfrom 10 to 500 μm and have an extent of ca. 1 mm and a depth of about100 μm.

Specifically in the presentation according to FIG. 4 a, there arises thealternative option, with a throughflow channel with no additionaldepressions, of providing for the accommodation of the lysis reagentsonly in the region 113 of the edges of the throughflow channel 111. Onthe other hand, in FIG. 4 b, such reagents, which in particular alsocontain magnetic beads for the binding of the DNA liberated, are evenlydistributed between the steps 112 across the throughflow channel 111.Magnetic beads have DNA- and protein-binding properties, if they havebeen appropriately pretreated. They can be coated with DNA-bindingproperties and if necessary also with antibodies. For the introductionof dry substances as a matrix with lysis reagent and magnetic beads,reference is in particular made to the applicant's prior DE 10 2004021780 A1 and prior DE 10 2004 021822.

FIGS. 5 to 7 show the structure of a PCR chamber 120 in the cartridgebase 101 with a flow channel 111. The valve arrangement for closure ofthe PCR chamber during use as intended is not shown here. It isessential that circular cylindrical depressions 124 and 124′ are presentin the PCR chamber 120 to accommodate specific reagents 127 and 127′,which are needed in the implementation of the PCR. Specifically in FIG.7, it is also shown that a dry, storable PCR reagent 127 or 127′,storable at room temperature, is firstly covered with a paraffin waxlayer 128 or 128′.

The correct implementation of the PCR with valve-controlledthermocycling within a cartridge is described in detail in theapplicant's parallel applications DE 10 2004 050576.4 and DE 10 2004050510.1 with the same application priority, to which in the presentconnection reference is expressly made (“Incorporation by Reference”).In particular, the use of magnetic beads for DNA binding andconcentration of the magnetic beads with the DNA in the PCR chamber 120by way of controllable magnetic fields is described therein, concerningwhich no more detailed description will be given here.

FIGS. 8 to 10 show the design and the structure of the ELISA reagentchannels 131 and 131′ of FIG. 1. Dish-shaped depressions 132 to 132^(6′) respectively are present, which are suitable to accommodatepre-dispensed and pre-apportioned quantities of reagents for the ELISAprocess according to FIG. 9. This has already been described in detailin WO 02/072262 A1, mentioned at the outset as state of the art, towhich in the present connection reference is also expressly made(“Incorporation by Reference”). In FIG. 10, the circular cylindricaldepressions 132 to 132 ^(6′) are shown filled with dry reagents 133 to133 ^(6′). Here a first reagent embodies a labeling enzyme and a secondreagent an enzyme substrate, such as is known to be needed in thehybridization of the sample, also prepared by a PCR if necessary, withspecific capture probes. In the detection zone 130, shown onlyschematically, different sensors for detection of biochemical reactionscan be located in a module of a noble metal/plastic composite.Especially during electrochemical measurements withsemiconductor-processed chips, i.e. in particular silicon-based sensors,the signals can be detected electrically and immediately furtherprocessed. Apart from the electrochemical measurement methods, magneticand/or piezo-electric measurement methods with corresponding sensors arealso possible.

In each of FIGS. 11 to 23, the cartridge 100 according to FIG. 1 isshown in top view, the zone of the cartridge 100 active in theanalytical process being marked in each: for this the cartridge 100 isinserted into an analytical device, which is not shown in detail in thediagrams and is not an object of the present patent application.

The evaluation is now illustrated on the basis of eleven concretecomponent process steps a) to m), after the cartridge has been insertedinto an evaluation device with at least one device for accommodating thecartridge, and the evaluation device with the cartridge immobilizedtherein has been activated. In detail, with reference to FIG. 1, thefollowing component steps are involved:

-   a) Ca. 10 μl of blood are introduced as the measurement sample. 1 μl    is automatically dispensed via the dispensing capillary 105.-   b) The excess blood is washed into the cavity 106 (waste 1).-   c) Next, 1 μl of blood sample is diluted with water and transferred    to the cell disintegration channel 110. There the cell    disintegration (lysis) of the blood cells and the binding of the    liberated DNA to the magnetic beads take place.-   d) Next, the magnetic beads are transferred to the PCR chamber and    collected there. A washing process takes place, the wash solution    being collected in the cavity 107 (waste 2).-   e) The washing process is now concluded.-   f) Next, the PCR chamber valves 122 and 122′ are closed and the PCR    is performed.-   g) During the PCR, the ELISA reagent channel 131 which contains the    enzyme substrate is simultaneously filled with water.-   h) Simultaneously during the PCR reaction, the ELISA reagent channel    131′ which contains the label enzyme is filled with water.-   i) After the PCR, the PCR chamber valves 122 and 122′ are opened and    the PCR product is passed via the detection module 130 where the    hybridization with the specific capture probes takes place (into    waste 3, channel 108).-   j) The enzyme substrate channel is vented into the waste channel 108    (waste 3).-   k) The label enzyme is vented into the waste channel 108 (waste 3).-   l) The label enzyme solution flows via the detection module 130 for    the labeling into the waste zone 109 (waste 4).-   m) The enzyme substrate solution flows via the detection module 130    for the enzymatic-electrochemical detection of the hybridization    into the waste zone 109 (waste 4).

Thereby the analytical process is concluded. In particular in the caseof electrochemical detection, the signals arising can be readelectrically and evaluated using a processor in accordance with a presetprogram.

The cartridge described in detail with channels and cavities in FIG. 1is produced from a polymeric material, such as for examplepolycarbonate, for example by injection molding technology. During this,the card base 101 with structures open upwards is first produced, andthe reagents are spotted into the initially open channels or cavitiesand then dried. The detection module is introduced in a suitable manner,in particular glued, into the cartridge. In conclusion, the channels andthe cavities are fitted for example with an elastic film as the uppercovering and is thus sealed for use as directed.

It is also possible to apply certain special fittings, for example assealing materials and/or venting materials onto the open card base 101before the closing and finishing of the cartridge on the cover side.

The specific measurement method is illustrated on the basis of FIGS. 11to 23 for one specific case of DNA analysis of a sample of whole blood.In general, the use of the cartridge described is envisaged for DNAanalysis on the one hand and/or protein analysis on the other, wherein,as already mentioned above, an appropriate reading device andcorresponding evaluation algorithm are utilized. Defined operatingmethods follow from this, which for the first time render the cartridgedescribed on the basis of the examples suitable in practice fordecentralized use in the context of a medical “Point of Care”application.

In conclusion, specifically for DNA analysis, the integrated operatingmethod for the cartridge described in detail above is once againsummarized as a combination or in the sequence of the individualcomponent steps:

-   -   introduction of the sample into the cartridge    -   insertion of the cartridge into the reading device    -   starting of the completely automatic assay        -   sample dispensing via dispensing section        -   washing of the dispensing section        -   dilution of the sample and introduction into lysis channel        -   residence in the lysis channel        -   collection of the DNA-bead complex by bead collectors in the            PCR chamber        -   washing of the DNA-bead complex with water        -   closure of the PCR chamber        -   implementation of the PCR        -   during the PCR: filling of both ELISA reagent channels with            water        -   opening of the PCR chamber        -   transport of the PCR product into detection chamber        -   hybridization in the detection chamber        -   venting of both ELISA reagent channels        -   filling and rinsing of the detection chamber with ELISA            reagent 1        -   filling and rinsing of the detection chamber with ELISA            reagent 2        -   implementation of the electrochemical measurements.

In the electrochemical measurements, firstly the rinsing of thedetection chamber with an antibody solution bearing an enzyme label(ELISA reagent 1) takes place. Then the rinsing of the detection chamberwith enzyme substrate (ELISA reagent 2) takes place. The electrochemicalmeasurements are performed in a manner in itself known at predefinable,different temperatures and variable flow rates of the enzyme-substratesolution.

For the protein analysis, corresponding procedures are used, but in thiscase the PCR is not used.

Example embodiments being thus described, it will be obvious that thesame may be varied in many ways. Such variations are not to be regardedas a departure from the spirit and scope of the present invention, andall such modifications as would be obvious to one skilled in the art areintended to be included within the scope of the following claims.

1. An arrangement for the integrated and automated DNA or proteinanalysis of a measurement sample in a single-use cartridge filled withdried reagents, the arrangement comprising: a system of at least one ofmicrochannels and microcavities for microfluidic process technology,present in the cartridge, the at least one of microchannels andmicrocavities including predefined geometric structures to accommodatereagents, wherein the reagents are stored ready in a storage-stable format defined sites in the at least one of microchannels and microcavitiesof the cartridge; and means for making the dry-stored reagents availablefor the relevant component process in suitable form.
 2. The arrangementas claimed in claim 1, wherein the structures include depressions toaccommodate the dry, storage-stable reagents.
 3. The arrangement asclaimed in claim 2, wherein the depressions include at least one stepwith step heights of 10 to 500 μm.
 4. The arrangement as claimed inclaim 2, wherein the depressions have a length of ca. 1 mm and a depthof about 100 μm.
 5. The arrangement as claimed in claim 3, wherein thedepressions are cylindrical, and wherein the length represents thediameter.
 6. The arrangement as claimed in claim 1, wherein the reagentsintroduced into the at least one of micro-channels and microcavitiesinclude the following properties: they are dryable substances withnegligible vapor pressure, which are stable at room temperature, so thatthe properties remain unchanged for one cell disintegration or one PCRor for the detection of biochemical quantities.
 7. The arrangement asclaimed in claim 1, wherein that mixtures of the particular substancewith additives form thin films which adhere to the walls.
 8. Thearrangement as claimed in claim 7, wherein the substances or mixturesintroduced into parts of the at least one of micro-channels andmicrocavities are watertightly covered with thin paraffin wax layers. 9.The arrangement as claimed in claim 1, wherein the substances introducedinto parts of the at least one of microchannels and microcavitiesinclude at least one of -DNA- and protein-binding properties.
 10. Thearrangement as claimed in claim 1, wherein the substances introducedinto parts of the at least one of microchannels and microcavities aremagnetic beads with specific binding properties.
 11. The arrangement asclaimed in claim 10, wherein the magnetic beads are coated withantibodies.
 12. The arrangement as claimed in claim 10, wherein themagnetic beads are coated with DNA-binding substances.
 13. Thearrangement as claimed in claim 1, wherein lysis reagents and magneticbeads are simultaneously present, and wherein the lysis reagents and themagnetic beads are contained in a single dry matrix.
 14. The arrangementas claimed in claim 1, wherein a so-called DNA ELISA assay or proteinELISA assay is performable, and wherein a label enzyme and an enzymesubstrate are present as reagents for the ELISA assay.
 15. Thearrangement as claimed in claim 1, wherein a detection module for theelectrical detection of the hybridization processes is present.
 16. Thearrangement as claimed in claim 15, wherein the detection moduleconsists of a noble metal/plastic composite.
 17. The arrangement asclaimed in claim 15, wherein the detection module consists of asemiconductor-processed silicon chip with noble metal electrodes. 18.The arrangement as claimed in claim 15, wherein at least one ofelectrochemical, magnetic and piezoelectric measurement methods are usedby the module for the electrical detection.
 19. The arrangement asclaimed in claim 1, wherein the cartridge includes an input port for awhole blood sample.
 20. The arrangement as claimed in claim 1, furthercomprising means for the introduction of water.
 21. The arrangement asclaimed in claim 20, further comprising an inlet port for connection toan external water source.
 22. The arrangement as claimed in claim 21,wherein the inlet port is connected to an integrated water reservoir.23. The arrangement as claimed in claim 1, wherein the at least one ofmicrochannels and microcavities are filled with dry buffer substances ofdefined ionic strength after addition of water.
 24. The arrangement asclaimed in claim 1, further comprising means for the mixing of wholeblood samples and water or the buffer solution.
 25. The arrangement asclaimed in claim 1, further comprising means for passing at least one ofblood, blood-water and blood-buffer mixture through the at least one ofthe microchannel and microcavity coated with lysis bead reagent.
 26. Thearrangement as claimed claim 1, further comprising means for generatinga magnetic field for the purpose of immobilizing at least one of theDNA/magnetic bead and protein/magnetic bead complex.
 27. The arrangementas claimed in claim 1, further comprising means for generating amagnetic field for the purpose of immobilizing the DNA/magnetic beadcomplex in a PCR cavity.
 28. The arrangement as claimed in claim 21,claim 1, further comprising means for closure of the PCR cavity.
 29. Thearrangement as claimed in claim 1, further comprising means for thethermocycling of the sample are present.
 30. The arrangement as claimedin claim 1, further comprising, in the cartridge, means for the storageof at least one of used sample material and used reagent.
 31. Thearrangement as claimed in claim 30, wherein the means for the storage ofat least one of used sample material and used reagents constitute wastereservoirs.
 32. The arrangement as claimed in claim 1, furthercomprising means for at least one of the germproof, particle- andcell-free venting of the waste reservoirs.
 33. The arrangement asclaimed in claim 1, further comprising means for the immobilization ofthe cartridge in a reading device.
 34. A method for the production of acartridge comprising: making from polymer, a cartridge base with atleast one of channels and cavities; spotting reagents into open channelsand drying the reagents there; and closing the at least one of channelsand cavities with a film.
 35. A production method as claimed in claim34, wherein the card base is produced by injection molding technology.36. The production method as claimed in claim 34, wherein specialmaterials are applied onto the card body.
 37. The production method asclaimed in claim 34, wherein, before the sealing of the card body, adetection module with measurement devices is introduced.
 38. Anoperating method for DNA analysis in an arrangement as claimed in claim1, the method comprising: introducing the sample into the cartridge;inserting the cartridge into the reading device; and starting a fullyautomatic assay.
 39. The operating method as claimed in claim 38,comprising the following steps during operation of the fully automaticassay: sample dispensing via a dispensing section; washing thedispensing section; diluting the measurement sample and introducing itinto the lysis channel; having a cell disintegration take place byresidence in the lysis channel; carrying the DNA-bead complex formedinto the PCR chamber by a liquid flow and holding it in the PCR chambervia a bead collector; washing of the DNA-bead complex with water;closing the PCR chamber is closed; performing the PCR; transporting,after completion of the PCR, the PCR product into the detection chamber;having hybridization processes, with specific capture probes, take placein the detection chamber; flushing the detection chamber with labelingenzyme; flushing the detection chamber with enzyme substrate; performingthe electrochemical measurement; and performing the electrochemicalmeasurements at various temperatures and various flow rates of theenzyme-substrate solution.
 40. The operating method as claimed in claim39, wherein, during the PCR, the ELISA reagent channels are filled withwater.
 41. The operating method as claimed in claim 39, wherein, afterthe hybridization, both ELISA channels are vented, that next thedetection chamber is firstly flushed gas bubble-free with the firstELISA reagent and then flushed gas bubble-free with the second ELISAreagent, and that the electrochemical measurement is then performed. 42.The operating method for protein analysis in an arrangement as claimedin claim 1, the method comprising: introducing the sample into thecartridge; inserting the cartridge into the reading device; and startingthe fully automatic assay.
 43. The operating method as claimed in claim42, with the following steps during operation of the fully automaticassay: sample dispensing via a dispensing section; washing thedispensing section; diluting the measurement sample and transporting itinto the detection chamber by a liquid flow; having binding processesbetween the proteins of the measurement sample and specific captureantibodies or capture proteins take place in the detection chamber;flushing the detection chamber with an antibody solution bearing anenzyme label (ELISA reagent 1); flushing the detection chamber withenzyme substrate (ELISA reagent 2); and performing the electrochemicalmeasurements.
 44. The operating method as claimed in claim 43, wherein,after the hybridization, both ELISA channels are vented, that next thedetection chamber is firstly flushed gas bubble-free with the firstELISA reagent and then flushed gas bubble-free with the second ELISAreagent, and that the electrochemical measurement is then performed. 45.The arrangement as claimed in claim 1, wherein the dry-stored reagentsare made available for the relevant component process as a liquidreagent.
 46. The arrangement as claimed in claim 20, wherein the meansfor the introduction of water includes an inlet port.
 47. Thearrangement as claimed in claim 1, further comprising an inlet port forthe introduction of water.
 48. The production method as claimed in claim36, wherein special materials include at least one of sealing membranesand venting membranes.